Project Summary Administrative Core This Phase II COBRE will continue our center?s work to develop molecular approaches for probing biology, to discover and apply new chemical biology tools for the study of biological pathways associated with disease, and to develop computational approaches for understanding small molecule interactions with complex macromolecular targets. Building on the infrastructure and successes of Phase I, our COBRE will develop new chemical biology tools for understanding the cellular and molecular mechanisms that bacterial pathogens use to survive and replicate inside host cells, molecular probes that can be used to understand Clp protease targets of infectious diseases, tools to map and understand the regulation of reversible mRNA modification by a ?methyl eraser? enzyme linked to the progression of human cancers, molecularly-defined nanoparticle adjuvants that yield specific immune responses in the lung to advance inhalable vaccine development, and computational approaches to elucidate the mechanisms by which small molecules regulate the structure and function of virus capsids. The goals of the Administrative Core are (1) Development of the administrative, fiscal and scientific aspects of the proposed COBRE, including establishment of a leadership team and a hiring plan; (2) Implementation of summative and formative evaluation strategies by the Leadership Team, an Internal Advisory Committee (IAC), mentors, and an External Advisory Committee (EAC); (3) Implementation of a Career Guidance Plan that enables faculty to develop successful research programs and to attract funding for their work; (4) Development of research, training & career development goals and capabilities. A plan for hiring and retaining successful faculty is detailed as is a plan for transitioning investigators to independent status with continued access to core facilities and participation in COBRE sponsored events.